tbuckley/cabot-search huggingface dataset:
Modern slavery in the United Kingdom: The illegal migration act risks undermining efforts to combat exploitation
Authors: Sian Oram
Journal: PLoS Medicine (2023)

The Illegal Migration Act, which recently passed through the United Kingdom (UK) parliament, poses a serious threat to the well-being of victims of modern slavery and efforts to combat exploitation. The Act gives the UK Government greater powers to deny support and allow the detention and deportation of potential victims and has been widely criticised, including by medical associations and charities. Measures included in the Act risk perpetuating the deprivation of safety, dignity, and medical care experienced by victims, instead of providing the protections to which they should be entitled.
Forthcoming Meetings
Authors: Jennie W Taylor
Journal: Neuro-Oncology (2023)

Journal Article Forthcoming Meetings Get access Jennie W Taylor Jennie W Taylor Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 25, Issue 9, September 2023, Page 1730, https://doi.org/10.1093/neuonc/noad139 Published: 05 September 2023 Article history Corrected and typeset: 05 September 2023 Published: 05 September 2023
Effectiveness of the BNT162b2 mRNA COVID-19 vaccine in children under 5 years
Authors: Christoph Strumann, Otavio Ranzani, Jeanne Moor, Reinhard Berner, Nicole Töpfner, Cho-Ming Chao, Matthias B. Moor
Journal: Journal of Clinical Investigation (2023)

To the Editor: Despite approval of the BNT162b2 mRNA vaccine (Pfizer/BioNTech vaccine Comirnaty) for children aged 6 months to 4 years by the European Medicines Agency (EMA) and the Federal Drug Administration (FDA) in 2022, little data on BNT162b2 vaccine effectiveness (VE) are available for this age group.We have retrospectively described the safety of BNT162b2 administered off-label in children younger than 5 years in Germany (1).Using data from this authentication-based retrospective survey obtained between April 14, 2022, and May 9, 2022 (1), we here report VE of BNT162b2 during an Omicron BA.1-2-dominant period.We analyzed 4,615 children, aged 2.8 ± 1.2 years (mean ± SD), who received their first dose of BNT162b2 on January 1, 2022, or thereafter (Supplemental Table 1 and Supplemental Figure 1; supplemental material available online with this article; https://doi.org/10.1172/JCI173329DS1).We used Cox regression to estimate relative VE of 2 BNT162b2 doses, as indicated in the Supplemental Methods.We used the period between the first and second vaccine dose as the reference period (24.8 ± 0.6 days) and the period ≥7 days after dose 2 to before dose 3 as the postvaccination period (59.5 ± 23.6 days).By this approach, the relative HR of SARS-CoV-2 infections was calculated after administration of 2 versus 1 dose of BNT162b2, and this was transformed to VE by the […]
Subclinical and clinical acute kidney injury share similar urinary peptide signatures and prognosis
Authors: Louis Boutin, Agnieszka Latosinska, Harald Mischak, Benjamin Deniau, Ayu Asakage, Matthieu Legrand, Etienne Gayat, Alexandre Mebazaa, Christos E. Chadjichristos, François Depret
Journal: Intensive Care Medicine (2023)
A clinical guide to rare male sexual disorders
Authors: Murat Gül, Mikkel Fode, Ahmet Urkmez, Paolo Capogrosso, Marco Falcone, Selcuk Sarikaya, Ioannis Sokolakis, Afonso Morgado, Andrey Morozov, Maarten Albersen, Giorgio Ivan Russo, Ege Can Serefoglu
Journal: Nature Reviews Urology (2023)
Heat exposure and hospitalizations for chronic kidney disease in China: a nationwide time series study in 261 major Chinese cities
Authors: Fu-Lin Wang, Wan-Zhou Wang, Fei-Fei Zhang, Su-Yuan Peng, Huai-Yu Wang, Rui Chen, Jin-Wei Wang, Peng-Fei Li, Yang Wang, Ming-Hui Zhao, Chao Yang, Lu-Xia Zhang
Journal: Military Medical Research (2023)

Abstract Background Climate change profoundly shapes the population health at the global scale. However, there was still insufficient and inconsistent evidence for the association between heat exposure and chronic kidney disease (CKD). Methods In the present study, we studied the association of heat exposure with hospitalizations for cause-specific CKD using a national inpatient database in China during the study period of hot season from 2015 to 2018. Standard time-series regression models and random-effects meta-analysis were developed to estimate the city-specific and national averaged associations at a 7 lag-day span, respectively. Results A total of 768,129 hospitalizations for CKD was recorded during the study period. The results showed that higher temperature was associated with elevated risk of hospitalizations for CKD, especially in sub-tropical cities. With a 1 °C increase in daily mean temperature, the cumulative relative risks ( RR ) over lag 0–7 d were 1.008 [95% confidence interval (CI) 1.003–1.012] for nationwide. The attributable fraction of CKD hospitalizations due to high temperatures was 5.50%. Stronger associations were observed among younger patients and those with obstructive nephropathy. Our study also found that exposure to heatwaves was associated with added risk of hospitalizations for CKD compared to non-heatwave days ( RR = 1.116, 95% CI 1.069–1.166) above the effect of daily mean temperature. Conclusions Short-term heat exposure may increase the risk of hospitalization for CKD. Our findings provide insights into the health effects of climate change and suggest the necessity of guided protection strategies against the adverse effects of high temperatures.
Identification of NOTCH-driven matrisome-associated genes as prognostic indicators of multiple myeloma patient survival
Authors: Daniela Simone Maichl, Julius Arthur Kirner, Susanne Beck, Wen-Hui Cheng, Melanie Krug, Martin Kuric, Carsten Patrick Ade, Thorsten Bischler, Franz Jakob, Dirk Hose, Anja Seckinger, Regina Ebert, Franziska Jundt
Journal: Blood Cancer Journal (2023)
<i>Mycobacterium tuberculosis</i>: Pathogenesis and therapeutic targets
Authors: Jiaxing Yang, Laiying Zhang, Wenliang Qiao, Youfu Luo
Journal: MedComm (2023)

Tuberculosis (TB) remains a significant public health concern in the 21st century, especially due to drug resistance, coinfection with diseases like immunodeficiency syndrome (AIDS) and coronavirus disease 2019, and the lengthy and costly treatment protocols. In this review, we summarize the pathogenesis of TB infection, therapeutic targets, and corresponding modulators, including first-line medications, current clinical trial drugs and molecules in preclinical assessment. Understanding the mechanisms of
Comparative Effectiveness of Upadacitinib Versus Ustekinumab for Ulcerative Colitis: A Multicenter Retrospective Cohort Study
Authors: Rahul S. Dalal, Govind Kallumkal, Heidy J. Cabral, Salam Bachour, Edward L. Barnes, Jessica R. Allegretti
Journal: Clinical Gastroenterology and Hepatology (2023)
Trends in heart failure between 2016 and 2022 in Türkiye (TRends-HF): a nationwide retrospective cohort study of 85 million individuals across entire population of all ages
Authors: Ahmet Celik, Dilek Ural, Anil Sahin, Inci Tugce Colluoglu, Emine Arzu Kanik, Naim Ata, Emre Arugaslan, Emre Demir, Mustafa Okan Ayvali, Mustafa Mahir Ulgu, Ahmet Temizhan, Yuksel Cavusoglu, Rezzan Deniz Acar, Sanem Nalbantgil, Lale Dinc Asarcikli, Selda Murat, Suayip Birinci, Mehmet Birhan Yilmaz
Journal: The Lancet Regional Health - Europe (2023)

Data on the burden of heart failure (HF) outside western countries are limited, but available data suggest it may present differently in other countries. The aim of this study was to examine the incidence, prevalence, and survival rates of HF in Türkiye, with a specific focus on how these rates vary according to age, sex, comorbidities, and socioeconomic status (SES).We harnessed the extensive National Electronic Database of the Turkish Ministry of Health, covering Turkey's entire population from January 1, 2016, to December 31, 2022, to identify 2,722,151 cases of HF and their associated comorbidities using ICD-10 codes. Analyzing the primary endpoint of all-cause mortality, our study utilized anonymized data to examine patient demographics, comorbidities, socioeconomic status, and survival patterns, employing statistical techniques to delve into relationships and trends. The data were segmented by gender, socioeconomic status, and age, involving cross-tabulations and statistical metrics to explore connections, odds ratios, and survival rates.The estimated prevalence of HF was 2.114% in Türkiye at the end of 2022, with an annual incidence ranging between 3.00 and 6.06 per 1000 person years. Females were older than males (69.8 ± 13.9 years vs. 66.8 ± 13.9 years, respectively). The most common comorbidities were congenital heart diseases and anemia under the age of 20, and hypertension and atherosclerotic cardiovascular disease in the adult population. Only 23.6% (643,159/2,722,151) of patients were treated with any triple guideline-directed medical therapy (GDMT) and 3.6% (96,751/2,722,151) of patients were on quadruple GDMT. The survival rates for patients with HF at 1, 5, and 7 years were 83.3% (95% CI: 83.2-83.3), 61.5% (95% CI: 61.4-61.6), and 57.7% (95% CI: 57.6-57.8) among females, and 82.1% (95% CI: 82.0-82.2), 58.2% (95% CI: 58.1-58.3), and 54.2% (95% CI: 54.0-54.3) among males. Despite a tendency for an increase from the highest to the lowest SES, the prevalence of HF and mortality were paradoxically lowest in the lowest SES region.The prevalence, incidence, and survival rates of HF in Türkiye were comparable to western countries, despite the notable difference of HF onset occurring 8-10 years earlier in the Turkish population. Drug usage statistics indicate there is a need for effective strategies to improve treatment with GDMT.None.
Determinants of the onset and prognosis of the post-COVID-19 condition: a 2-year prospective observational cohort study
Authors: Lourdes Mateu, Cristian Tebe, Cora Loste, José Ramón Santos, Gemma Lladós, Cristina López, Sergio España-Cueto, Ruth Toledo, Marta Font, Anna Chamorro, Francisco Muñoz-López, Maria Nevot, Nuria Vallejo, Albert Teis, Jordi Puig, Carmina R. Fumaz, José A. Muñoz-Moreno, Anna Prats, Carla Estany-Quera, Roser Coll-Fernández, Cristina Herrero, Patricia Casares, Ana Garcia, Bonaventura Clotet, Roger Paredes, Marta Massanella
Journal: The Lancet Regional Health - Europe (2023)

At least 5-10% of subjects surviving COVID-19 develop the post-COVID-19 condition (PCC) or "Long COVID". The clinical presentation of PCC is heterogeneous, its pathogenesis is being deciphered, and objective, validated biomarkers are lacking. It is unknown if PCC is a single entity or a heterogeneous syndrome with overlapping pathophysiological basis. The large US RECOVER study identified four clusters of subjects with PCC according to their presenting symptoms. However, the long-term clinical implications of PCC remain unknown.We conducted a 2-year prospective cohort study of subjects surviving COVID-19, including individuals fulfilling the WHO PCC definition and subjects with full clinical recovery. We systematically collected post-COVID-19 symptoms using prespecified questionnaires and performed additional diagnostic imaging tests when needed. Factors associated with PCC were identified and modelled using logistic regression. Unsupervised clustering analysis was used to group subjects with PCC according to their presenting symptoms. Factors associated with PCC recovery were modelled using a direct acyclic graph approach.The study included 548 individuals, 341 with PCC, followed for a median of 23 months (IQR 16.5-23.5), and 207 subjects fully recovered. In the model with the best fit, subjects who were male and had tertiary studies were less likely to develop PCC, whereas a history of headache, or presence of tachycardia, fatigue, neurocognitive and neurosensitive complaints and dyspnea at COVID-19 diagnosis predicted the development of PCC. The cluster analysis revealed the presence of three symptom clusters with an additive number of symptoms. Only 26 subjects (7.6%) recovered from PCC during follow-up; almost all of them (n = 24) belonged to the less symptomatic cluster A, dominated mainly by fatigue. Recovery from PCC was more likely in subjects who were male, required ICU admission, or had cardiovascular comorbidities, hyporexia and/or smell/taste alterations during acute COVID-19. Subjects presenting with muscle pain, impaired attention, dyspnea, or tachycardia, conversely, were less likely to recover from PCC.Preexisting medical and socioeconomic factors, as well as acute COVID-19 symptoms, are associated with the development of and recovery from the PCC. Recovery is extremely rare during the first 2 years, posing a major challenge to healthcare systems.Fundació Lluita contra les Infeccions.
Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy
Authors: Letong Cai, Yuchen Li, Jiaxiong Tan, Ling Xu, Yangqiu Li
Journal: Journal of Hematology & Oncology (2023)

Abstract In one decade, immunotherapy based on immune checkpoint blockades (ICBs) has become a new pillar of cancer treatment following surgery, radiation, chemotherapy, and targeted therapies. However, not all cancer patients benefit from single or combination therapy with anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies. Thus, an increasing number of immune checkpoint proteins (ICPs) have been screened and their effectiveness evaluated in preclinical and clinical trials. Lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain-containing-3 (TIM-3), and T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) constitute the second wave of immunotherapy targets that show great promise for use in the treatment of solid tumors and leukemia. To promote the research and clinical application of ICBs directed at these targets, we summarize their discovery, immunotherapy mechanism, preclinical efficiency, and clinical trial results in this review.
Genetic Variants That Impact Alternative Polyadenylation in Cancer Represent Candidate Causal Risk Loci
Authors: Bin Li, Yimin Cai, Can Chen, Gaoyuan Li, Ming Zhang, Zequn Lu, Fuwei Zhang, Jinyu Huang, Linyun Fan, Caibo Ning, Yanmin Li, Wenzhuo Wang, Hui Geng, Yizhuo Liu, Shuoni Chen, Hanting Li, Shuhui Yang, Heng Zhang, Wen Tian, Zhongchao Zhu, Bin Xu, Heng Li, Haijie Li, Meng Jin, Xiaoyang Wang, Shaokai Zhang, Jiuyang Liu, Chaoqun Huang, Xiaojun Yang, Yongchang Wei, Ying Zhu, Jianbo Tian, Xiaoping Miao
Journal: Cancer Research (2023)

Abstract Alternative polyadenylation (APA) is emerging as a major mechanism of posttranscriptional regulation. APA can impact the development and progression of cancer, suggesting that the genetic determinants of APA might play an important role in regulating cancer risk. Here, we depicted a pan-cancer atlas of human APA quantitative trait loci (apaQTL), containing approximately 0.7 million apaQTLs across 32 cancer types. Systematic multiomics analyses indicated that cancer apaQTLs could contribute to APA regulation by altering poly(A) motifs, RNA-binding proteins (RBP), and chromatin regulatory elements and were preferentially enriched in genome-wide association studies (GWAS)–identified cancer susceptibility loci. Moreover, apaQTL-related genes (aGene) were broadly related to cancer signaling pathways, high mutational burden, immune infiltration, and drug response, implicating their potential as therapeutic targets. Furthermore, apaQTLs were mapped in Chinese colorectal cancer tumor tissues and then screened for functional apaQTLs associated with colorectal cancer risk in 17,789 cases and 19,951 controls using GWAS-ChIP data, with independent validation in a large-scale population consisting of 6,024 cases and 10,022 controls. A multi-ancestry–associated apaQTL variant rs1020670 with a C&amp;gt;G change in DNM1L was identified, and the G allele contributed to an increased risk of colorectal cancer. Mechanistically, the risk variant promoted aberrant APA and facilitated higher usage of DNM1L proximal poly(A) sites mediated by the RBP CSTF2T, which led to higher expression of DNM1L with a short 3′UTR. This stabilized DNM1L to upregulate its expression, provoking colorectal cancer cell proliferation. Collectively, these findings generate a resource for understanding APA regulation and the genetic basis of human cancers, providing insights into cancer etiology. Significance: Cancer risk is mediated by alternative polyadenylation quantitative trait loci, including the rs1020670-G variant that promotes alternative polyadenylation of DNM1L and increases colorectal cancer risk.
Safety, tolerability, pharmacokinetics and efficacy of HB0017, a humanized monoclonal antibody that targets interleukin-17A, in healthy participants and patients with moderate-to-severe plaque psoriasis
Authors: Congjun Jiang, Yu Du, Xiaoyan Liu, Jingjing Wang, Cuizhu Ge, Jingyue Xu, Shuoxiong Wang, Benke Li, Gege Zhu, Wanlu Zhang, Qiaoxiao Qian, Chi Ma, Xiangyang Zhu, Yifan Zhan, Yongmin Yang
Journal: British Journal of Dermatology (2023)

Abstract Background Several interleukin (IL)-17 inhibitors have been approved for the treatment of moderate-to-severe plaque psoriasis (PsO). There is still scope for the development of affordable treatments for PsO. Objectives To assess, in a phase Ia study, the safety, tolerability and pharmacokinetics (PK) of HB0017, a humanized monoclonal antibody that targets IL-17A, in healthy participants and patients with moderate-to-severe plaque PsO; and, in a phase Ib study, to assess the efficacy of HB0017 in patients with moderate-to-severe plaque PsO. Methods The phase Ia study (NCT04505033) was a randomized double-blind placebo-controlled dose-escalation study in healthy participants. Each cohort of 10 volunteers was randomly assigned to receive either a single dose of HB0017 (50 mg, 150 mg, 300 mg or 450 mg) or the matching placebo at a ratio of 4 : 1. The phase Ib study (NCT05442788) was a randomized double-blind placebo-controlled dose-escalation study in enrolled patients with moderate-to-severe plaque PsO. Each cohort of 10 patients was randomly assigned to receive either multiple doses of HB0017 (150 mg, 300 mg or 450 mg) or the matching placebo at a ratio of 4 : 1. Results HB0017 demonstrated dose-proportional linear PK and was tolerated across the dose range assessed. In the phase Ia and Ib studies, participants in both the HB0017 and placebo groups experienced treatment-emergent adverse events (69% vs. 87%, 96% vs. 100%, respectively). HB0017 demonstrated clinically meaningful effects in patients with moderate-to-severe plaque PsO. PASI 75 [≥ 75% improvement in Psoriasis Area and Severity Index (PASI)], PASI 90 (≥ 90% improvement in PASI) and static Physician Global Assessment (sPGA) 0/1 (i.e. ‘clear’ or ‘almost clear’) responses were 100% for the HB0017 300-mg group, with maximal improvements (100% or near 100% reductions from baseline) in PASI score observed at week 12, while the duration of effect was evident up to week 20. There was no clinical response in any participant in the placebo group in the phase Ib study. Conclusions Overall, HB0017 showed acceptable safety and tolerability in both healthy participants and patients with moderate-to-severe plaque PsO. An encouraging signal of efficacy with a longer half-life provides HB0017 with the potential to be added to the currently available range of biologics targeting IL-17A.
Onychomycosis not associated with poor COVID-19 clinical outcomes in a retrospective cohort study at an academic institution, New York, New York
Authors: Kaya L. Curtis, Rhiannon C. Miller, Amar D. Desai, Shari R. Lipner
Journal: Journal of the American Academy of Dermatology (2023)

To the Editor: Nail findings, including Beau's lines, leukonychia, and splinter hemorrhages may be clues to underlying systemic diseases.1 Nail changes are rarely prognostic indicators, with the exception of metastases to the nail.2 However, a retrospective cohort study by Rakita et al3 reported that onychomycosis was associated with more severe COVID-19 clinical outcomes. Therefore, we aimed to evaluate COVID-19 outcomes in onychomycosis patients using patients with other onychodystrophies as controls.
Reducing branched-chain amino acids improves cardiac stress response in mice by decreasing histone H3K23 propionylation
Authors: Zhi Yang, Minzhen He, Julianne Austin, Danish Sayed, Maha Abdellatif
Journal: Journal of Clinical Investigation (2023)

Identification of branched-chain amino acid (BCAA) oxidation enzymes in the nucleus led us to predict that they are a source of the propionyl-CoA that is utilized for histone propionylation and, thereby, regulate gene expression. To investigate the effects of BCAAs on the development of cardiac hypertrophy and failure, we applied pressure overload on the heart in mice maintained on a diet with standard levels of BCAAs (BCAA control) versus a BCAA-free diet. The former was associated with an increase in histone H3K23-propionyl (H3K23Pr) at the promoters of upregulated genes (e.g., cell signaling and extracellular matrix genes) and a decrease at the promoters of downregulated genes (e.g., electron transfer complex [ETC I-V] and metabolic genes). Intriguingly, the BCAA-free diet tempered the increases in promoter H3K23Pr, thus reducing collagen gene expression and fibrosis during cardiac hypertrophy. Conversely, the BCAA-free diet inhibited the reductions in promoter H3K23Pr and abolished the downregulation of ETC I-V subunits, enhanced mitochondrial respiration, and curbed the progression of cardiac hypertrophy. Thus, lowering the intake of BCAAs reduced pressure overload-induced changes in histone propionylation-dependent gene expression in the heart, which retarded the development of cardiomyopathy.
E-cigarette vapor renders neutrophils dysfunctional due to filamentous actin accumulation
Authors: Alice E. Jasper, Aduragbemi A. Faniyi, Lauren C. Davis, Frances S. Grudzinska, Robyn Halston, Jon Hazeldine, Dhruv Parekh, Elizabeth Sapey, David R. Thickett, Aaron Scott
Journal: Journal of Allergy and Clinical Immunology (2023)

Electronic cigarette (e-cigarette) use continues to rise despite concerns of long-term effects, especially the risk of developing lung diseases such as chronic obstructive pulmonary disease. Neutrophils are central to the pathogenesis of chronic obstructive pulmonary disease, with changes in phenotype and function implicated in tissue damage.